细胞表面相关蛋白黏蛋白 15（MUC15）在子痫前期中升高。

Cell surface associated protein mucin 15 (MUC15) is elevated in preeclampsia.

机构信息

The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia.

出版信息

Placenta. 2023 Sep 7;140:39-46. doi: 10.1016/j.placenta.2023.07.013. Epub 2023 Jul 20.

DOI:10.1016/j.placenta.2023.07.013

PMID:37531748

Abstract

BACKGROUND

Mucins are a family of proteins that protect the epithelium. A particular type of mucin, MUC15 is highly expressed in the placenta. This study aimed to characterise MUC15 in preeclampsia and investigate its role in placental stem cell biology.

METHODS

MUC15 mRNA and protein were measured in placentas from patients with early onset (<34 weeks' gestation) preeclampsia. Circulating serum MUC15 was measured via ELISA. MUC15 was localised in the placenta using in situ hybridisation. MUC15 mRNA expression was measured across differentiation of human trophoblast stem cells (hTSCs) to syncytiotrophoblast and extravillous trophoblasts. MUC15 was measured after syncytialised hTSCs were cultured in hypoxic (1% O) and proinflammatory (TNF α, IL-6) conditions. MUC15 secretion was assessed when syncytialised hTSCs were treated with brefeldin A (impairs protein trafficking) and batimastat (inhibits matrix metalloproteinases).

RESULTS

MUC15 protein was significantly increased in the placenta (P = 0.0003, n = 32 vs n = 20 controls) and serum (P = 0.016, n = 32 vs n = 22 controls) of patients with preeclampsia, whilst MUC15 mRNA remained unchanged (n = 61 vs n = 18 controls). MUC15 mRNA (P = 0.005) and protein secretion (P = 0.006) increased following differentiation to syncytiotrophoblast cells. In situ hybridisation confirmed MUC15 localised to the syncytiotrophoblast cell within the placenta. Neither hypoxic or inflammatory conditions changed MUC15 mRNA expression or secretion. Brefeldin A treated hTSCs did not alter MUC15 secretion, whilst batimastat reduced MUC15 secretion (P = 0.044).

CONCLUSIONS

MUC15 is increased in early onset preeclampsia and is cleaved by matrix metalloproteinases. Increased MUC15 may reflect a protective mechanism associated with placental dysfunction. Further research will aid in confirming this.

摘要

背景

黏蛋白是一组保护上皮细胞的蛋白质。一种特殊类型的黏蛋白，MUC15 在胎盘组织中高度表达。本研究旨在对早发型（<34 周妊娠）子痫前期中的 MUC15 进行特征分析，并研究其在胎盘干细胞生物学中的作用。

方法

用酶联免疫吸附试验（ELISA）法检测早发型子痫前期患者胎盘组织中 MUC15mRNA 和蛋白的表达水平。用原位杂交法定位胎盘组织中的 MUC15。检测人滋养层干细胞（hTSCs）向合胞体滋养层和绒毛外滋养层分化过程中 MUC15mRNA 的表达。将 hTSCs 融合后在低氧（1% O2）和促炎（TNFα、IL-6）条件下培养，测定 MUC15 的表达水平。用布雷非德菌素 A（抑制蛋白转运）和巴替玛司他（抑制基质金属蛋白酶）处理融合的 hTSCs 后，测定 MUC15 的分泌情况。

结果

早发型子痫前期患者胎盘组织中 MUC15 蛋白的表达明显升高（P=0.0003，n=32 与 n=20 对照组），血清中 MUC15 蛋白的表达也升高（P=0.016，n=32 与 n=22 对照组），而 MUC15mRNA 不变（n=61 与 n=18 对照组）。hTSCs 向合胞体滋养层细胞分化后，MUC15mRNA（P=0.005）和蛋白分泌（P=0.006）均增加。原位杂交证实 MUC15 定位于胎盘内的合胞体滋养层细胞。低氧或炎症条件均未改变 MUC15mRNA 的表达或分泌。布雷非德菌素 A 处理 hTSCs 并未改变 MUC15 的分泌，而巴替玛司他降低了 MUC15 的分泌（P=0.044）。